{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:02:10Z","timestamp":1790604130580,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS119538"],"award-info":[{"award-number":["R01NS119538"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS125262"],"award-info":[{"award-number":["R01NS125262"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01NS119538"],"award-info":[{"award-number":["R01NS119538"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01NS125262"],"award-info":[{"award-number":["R01NS125262"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vascular dementia (VaD) is a leading cause of cognitive decline and arises from heterogeneous cerebrovascular pathologies, most commonly cerebral small vessel disease and chronic cerebral hypoperfusion. Microglia, the brain\u2019s resident immune cells, exert a dual, stage-dependent influence during VaD progression, initially supporting neuroprotection through debris clearance and tissue repair, but later contributing to chronic neuroinflammation, synaptic loss, and white matter injury. Emerging evidence suggests that multiple molecular pathways, including purinergic receptors, Toll-like receptors and inflammasome cascades, complement-mediated synaptic pruning, and homeostatic and metabolic regulators, such as TREM2 (triggering receptor expressed on myeloid cells 2) and CSF1R (colony-stimulating factor 1 receptor), govern microglial functional transitions. Furthermore, post-transcriptional regulation by microRNAs (e.g., miR-30 family, miR-124, miR-146a, and miR-155) modulates these phenotypes, offering potential biomarkers and therapeutic targets. Understanding these interconnected molecular and epigenetic networks provides a framework for reprogramming microglia from pro-inflammatory to reparative states, thereby providing a mechanistic basis for precision interventions to preserve neurovascular integrity and mitigate cognitive impairment in VaD.<\/jats:p>","DOI":"10.3390\/ijms27093719","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:54:08Z","timestamp":1776862448000},"page":"3719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microglial Plasticity in Vascular Dementia: Mechanisms and Therapeutic Reprogramming"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7957-2815","authenticated-orcid":false,"given":"Manish","family":"Shukla","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarvis","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Jiangsu Province Hospital of Integrated Chinese and Western Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210028, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5389-0066","authenticated-orcid":false,"given":"Rong","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Penn State Neuroscience Institute, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Penn State Neuroscience Institute, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2025). 2025 Alzheimer\u2019s Disease Facts and Figures. 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